Research

Overview

We use the whole gamut of modern techniques -- molecular, cellular, biochemical, proteomic, genomic,
bioinformatic -- to investigate the role of the transcription factor HNF4 in physiology and disease
with particular emphasis on cancer and diabetes. In so doing, we aim to shed light on the molecular
mechanisms of tissue-specific gene regulation, the dichotomy between cellular differentiation and
proliferation, and the role of transcription regulation and alternative splicing and promoter usage
in human evolution.

Current Projects

Ligand Binding

Identify the endogenous ligand for HNF4

Characterize the function of ligand binding

HNF4 Isoforms

Characterize the functional differences between the various HNF4 splice variants

Determine the physiological effects of those splice variants in different tissues using in vivo and in vitro models

Post-translational modifications

Identify and characterize the post translational modifications in HNF4

Identify the relevant modifying enzymes and signaling pathways

Genome-wide analysis of nuclear receptor target genes

Use the latest tools in bioinformatics and genomics to identify all the HNF4 target genes in the
human and mouse genomes

Use protein binding matrices and bioinformatics to develop a network of target genes for HNF4 and
other nuclear receptors

Funding

We gratefully acknowledge past and present funding from a variety of
state and federal agencies including the California Breast Cancer
Research Coordinating Committee, the UC Toxic Substances Research and
Training Grant, the American Heart Association, the National Science
Foundation and the National Institutes of Health.